Coxiella burnetti avoids macrophage phagocytosis by interfering with spatial distribution of complement receptor 3
Coxiella burnetti avoids macrophage phagocytosis by interfering with spatial distribution of complement receptor 3
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DOI：
10.4049/jimmunol.170.8.4217
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发表时间：
2003-04-15
影响因子：
4.4
通讯作者：
Mege, JL
中科院分区：
文献类型：
--
作者：
Capo, C;Moynault, A;Mege, JL
吞噬作用是一种高度局部化的事件，需要形成空间和时间受限的信号。许多微生物利用这一特性入侵宿主细胞。柯克斯伯氏杆菌是Q热的病原体，是一种专性细胞内细菌，它已经开发出一种基于颠覆受体介导的吞噬作用的巨噬细胞生存策略。C Burnetti的摄取由α(V)β(3)、整合素介导，并受α(V)β(3)、整合素和补体受体3(CR3)(CD11b/CD18)的干扰所限制。在这项研究中，我们发现CR3分子保留在由C.Burnetti诱导的THP-1单核细胞伪足延伸之外，尽管α(V)β(3)整合素存在于伪足中。RANTES等化学诱导剂将CR3定位恢复到伪足延伸的前方，并增加了伯内蒂弧菌的吞噬作用，表明CR3的定位对细菌摄取至关重要。此外，由于HIV-1Nef蛋白的表达而引起的单核细胞激活也通过允许CR3重新分布到细菌诱导的伪足来恢复CR3介导的伯内蒂芽胞杆菌的吞噬作用。RANTES刺激或表达Nef的THP-1细胞中CR3的重新分布和Burnetti弧菌吞噬功能的增强与抑制Burnetti弧菌的细胞内复制有关。因此，CR3的定位对于细菌吞噬和控制细菌复制都是至关重要的。这项研究描述了一种未被报道的基于单核细胞受体定位改变的吞噬颠覆细胞内病原体的策略。
Phagocytosis is a highly localized event requiring the formation of spatially and temporally restricted signals. Numerous microorganisms have taken advantage of this property to invade host cells. Coxiella burnetti, the agent of Q fever, is an obligate intracellular bacterium that has developed a survival strategy in macrophages based on subversion of receptor-mediated phagocytosis. The uptake of C burnetti is mediated by alpha(v)beta(3), integrin and is restricted by impaired cross-talk of alpha(v)beta(3), integrin and complement receptor 3 (CR3) (CD11b/CD18). In this study, we showed that CR3 molecules remained outside the pseudopodal extensions induced by C. burnetti in THP-1 monocytes, although alpha(v)beta(3) integrin was present in the pseudopods. Chemoattractants such as RANTES restored CR3 localization to the front of pseudopodal extensions and increased C. burnetti phagocytosis, demonstrating that the localization of CR3 is critical for bacterial uptake. In addition, monocyte activation due to the expression of HIV-1 Nef protein also restored CR3-mediated phagocytosis of C burnetti by allowing CR3 redistribution toward bacterial-induced pseudopods. The redistribution of CR3 and increased C. burnetti phagocytosis in THP-1 cells stimulated by RANTES or expressing Nef were associated with the inhibition of intracellular replication of C. burnetti. Hence, the localization of CR3 is critical for bacterial phagocytosis and also for the control of bacterial replication. This study describes a nonpreviously reported strategy of phagocytosis subversion by intracellular pathogens based on altered localization of monocyte receptors.